CN107917942B

CN107917942B - Electrode system and test strip and instrument containing same

Info

Publication number: CN107917942B
Application number: CN201610889253.8A
Authority: CN
Inventors: 赵天贤; 张仑; 许文文; 周芳芳
Original assignee: Helixgen (guangzhou) Co ltd
Current assignee: Helixgen (guangzhou) Co ltd
Priority date: 2016-10-11
Filing date: 2016-10-11
Publication date: 2021-06-18
Anticipated expiration: 2036-10-11
Also published as: CN107917942A

Abstract

The invention discloses an electrode system, which comprises at least two electrodes, wherein one electrode is a working electrode, and the other electrode is a reference electrode. The working electrode is of a sheet structure, and the reference electrode is of a non-closed ring structure arranged around the working electrode; preferably, the sheet-like structure is a regular or irregular circle or polygon; the non-closed ring structure is a regular or irregular circular ring or a polygonal ring.

Description

Electrode system and test strip and instrument containing same

Technical Field

The invention relates to an electrode, in particular to an electrode for detecting blood coagulation time.

Background

Electrochemical sensors have been widely used for detecting various clinical parameters such as blood sugar, blood coagulation, blood gas, blood electrolyte and the like, and are particularly suitable for detecting the blood coagulation time. The Prothrombin Time (PT) and the international normalized ratio INR are determined by measuring the release of thrombin during coagulation using electrochemical methods. The assay is carried out in two steps, the first being the contacting of a blood sample with a reagent in which thromboplastin causes the blood to undergo a clotting reaction to produce thrombin which reacts with a substrate in the reagent to produce an oxidizable material. The second process is that the analyzer applies a direct current voltage between the working electrode and the reference electrode to oxidize the oxidizable substance to generate a current, and the blood coagulation time is calculated by analyzing the oxidation current curve.

Chinese utility model CN102818822A discloses a device for measuring blood coagulation time by measuring the electrical impedance change of blood generated during blood coagulation, which comprises one or more pairs of electrodes made of materials including but not limited to carbon, gold, silver, copper, carbon, silver, palladium, platinum, nickel, other similar materials or any combination of the above materials, and is used for connecting the circuit between blood and a detecting instrument. The electrodes used to detect prothrombin time are a pair of electrodes arranged in parallel, this electrode arrangement is also common in electrochemical sensors. One disadvantage of this design is that the reproducibility of the reagent spotting is not ideal, and therefore the accuracy of the measurement is compromised, since no part frames the reagent.

Chinese patent CN2788184Y discloses a biological test strip, which relates to a biological test strip for detecting the concentration of blood ketone body or glucose in whole blood, comprising: the device comprises a substrate carrying electrodes, a reaction area space provided with a reaction reagent, a hydrophilic cover plate and a spacing layer between the substrate and the hydrophilic cover plate; wherein the electrodes comprise strip-shaped working electrodes and strip-shaped reference electrodes; the spacing layer is provided with a groove with one side opened; the reaction area space is formed by limiting the spacing layer with grooves, the substrate and the hydrophilic cover plate, and is provided with a sample inlet hole and an exhaust hole. The exhaust hole is positioned on the hydrophilic cover plate. The structure of the biological test strip is a common mode of the prior related test strips.

Disclosure of Invention

In order to overcome the shortcomings of the prior art, the invention provides an electrode.

The electrode provided by the invention is particularly suitable for detecting prothrombin. The reproducibility is good, and the production process is simple.

The invention is realized by the following technical scheme:

the invention provides an electrode system, which comprises two or more electrodes, wherein one electrode is a working electrode, and the other electrode is a reference electrode; the working electrode is of a sheet structure, and the reference electrode comprises a non-closed ring structure arranged around the working electrode; preferably, the sheet-like structure is a regular or irregular circle or polygon; the non-closed ring structure is a regular or irregular circular ring or a polygonal ring.

The non-closed ring structure is a non-closed ring structure with an opening; preferably, it has a circular ring shape with one opening.

In one embodiment, the working electrode is a circular or approximately circular sheet structure, and the reference electrode is a non-closed ring structure concentrically arranged with the working electrode.

The non-closed loop structure means that the reference electrode is arranged in a circular (or approximately circular) path, and one end of the reference electrode is not connected with the other end of the reference electrode, so that a circular shape with an opening is defined.

The size of the opening depends on the electrode manufacturing technology, and if a high-precision technology such as a chemical etching method or a laser cutting method is adopted, the width of the opening can be as small as 0.1 mm; if a low precision technique such as silk-screen printing is used, the opening width needs to be larger, typically above 1 mm. The smaller the opening, the better, the function of which is primarily to let through the leads connecting the working electrodes located therein. The size of the opening depends on the electrode fabrication technique employed, and can be as small as 0.1mm if a high precision technique such as chemical etching or laser cutting is employed; if low precision techniques such as silk screening are used, the openings need to be larger, typically above 1 mm.

The inner diameter of the circular ring is 1 mm-10 mm, and the outer diameter is 2 mm-12 mm; the diameter of the circular working electrode is 0.5 mm-9 mm.

Preferably, the circular working electrode and the reference electrode with the non-closed ring structure both have certain thicknesses, and the thicknesses are respectively 0.01 mm-0.1 mm and 0.05-0.5 mm. The thickness refers to the level of protrusion from the substrate.

The material of the working electrode is selected from inert metal or carbon; the material of the reference electrode is selected from silver/silver chloride; more preferably, the material of the working electrode is selected from gold, platinum, rhodium and carbon; more preferably, the material of the working electrode is selected from carbon.

Ag/AgCl electrode material refers to a mixture of silver and silver chloride, typically in a ratio between 10%/90% and 50%/50%.

The electrode pair formed by matching the sheet-shaped working electrode and the non-closed-loop reference electrode has the advantages that: the reference electrode of the non-closed ring is used as a limiting part of the reaction reagent under the condition of not adding an additional part, so that the repeatability of reagent spotting is improved, and the test precision is improved. In addition, the electrode structure can directly contact the reactant on the working electrode to increase the efficiency of the electrochemical reaction.

The reaction reagent mainly comprises thromboplastin, thrombin substrate, film forming agent, preservative and the like. The components are dissolved in the buffer solution to form a reagent mixed solution, then the reagent mixed solution is spotted into the inner diameter of the non-closed annular structure by a proper spotting method such as contact or spray, the surface of the electrode and the surface of the substrate around the electrode are attached with the reagent, and finally the reagent is dried and solidified to form a layer of dry reagent film on the working electrode and the periphery of the working electrode.

Due to the thickness and the hydrophobicity of the non-closed ring reference electrode, the reagent mixed solution does not overflow and is limited within the inner diameter of the reference electrode when being spotted, and a uniform membrane can be formed after drying, so that the reaction repeatability of the test strip is enhanced.

The invention adopts carbon or inert metal as working electrode and Ag/AgCl as reference electrode respectively in cooperation with the electrodes arranged in the non-closed ring structure and the circular structure; it is particularly preferred to use carbon as the working electrode and Ag/AgCl as the reference electrode. Both materials may be printed onto the substrate by screen printing. Because the silk-screen technology is very simple, the electrode system manufactured according to the invention can achieve low cost.

The invention also provides a substrate containing the electrode, or a test strip further assembled.

The substrate is made of insulating materials.

Preferably, the substrate is further provided with two conductive wires respectively connected with the working electrode and the reference electrode; more preferably, the two conductive wires are respectively connected with two conductive contact plates;

more preferably, the reference electrode is further provided with a protrusion located at any position of the non-closed loop structure, and the protrusion is used for connecting a conductive wire.

The detection test strip comprises an insulating substrate loaded with the electrode, and a chemical reagent is loaded in a non-closed ring structure of the reference electrode on the insulating substrate; preferably, the chemical reagent is formed by spotting and drying a liquid reagent.

The detection object of the test strip is a liquid sample; more preferably, the liquid sample is a blood sample.

In an alternative embodiment, the strip further comprises a channel plate disposed above the base plate, and a cover plate disposed above the channel plate; the channel plate is provided with a channel plate hollow structure which is positioned above the non-closed ring structure and has an area larger than that of the non-closed ring structure; the space defined by the hollow structure of the channel plate and positioned on the substrate is a reaction area.

Or, as another alternative embodiment, the test strip further comprises an elevating sheet on the base plate, a channel plate on the elevating sheet, and a cover plate on the channel plate; the heightening sheet is provided with a hollow structure of the heightening sheet, the hollow structure of the heightening sheet is positioned above the non-closed ring structure, and the area of the hollow structure of the heightening sheet is larger than that of the non-closed ring structure; the channel plate is provided with a channel plate hollow structure corresponding to the heightening piece hollow structure in position; the space defined by the hollow-out structures of the heightening pieces and positioned on the substrate is a reaction area.

The reaction area is the area where the blood sample finally enters and reacts with the area (e.g., coagulation reaction).

The test strip of the present invention may have a structure other than the electrode system described above, such as a cover plate, a channel plate, a base plate, etc., which is a structure other than the electrode system disclosed in CN 2788184Y. Alternatively, these portions may be of improved construction.

As an example of the improved structure, the structure of the cover plate and the passage plate of the present invention may be as follows.

One end of the cover plate of the test strip is provided with a sample inlet hole, and the other end is provided with an air outlet; the channel plate is provided with a sample injection cavity, a liquid circulation channel and a circulation hole, wherein when the cover plate is stacked on the channel plate, the sample injection cavity is positioned below the sample injection hole and is connected with the circulation hole through the liquid circulation channel;

preferably, the aperture of the air outlet is 0.1mm-5 mm; preferably, the ratio of the cross-sectional area of the extension pipe to the cross-sectional area of the liquid flow channel is from 1:1 to 1: 10;

preferably, the ratio of the length of the extension conduit to the length of the liquid flow channel is from 1:1 to 1: 10;

preferably, at least part of the tube wall of the liquid communication channel is made of hydrophilic materials, and the hydrophilic material part penetrates through two ends of the liquid communication channel;

preferably, the pipe wall of the extension pipe is at least partially made of hydrophobic material; preferably a hydrophobic material is present near the outlet portion and a hydrophilic material is present near the flow-through hole portion, the length of the hydrophilic material portion preferably being 1-2 mm.

Preferably, the sample injection cavity, the liquid circulation channel, the circulation hole, the extension pipeline and the vent are all located on the same straight line;

preferably, the distance between the air vent and the tail end is 1 mm-10 mm; preferably, the area ratio of the air vent to the sampling hole is 1: 1-1: 100.

The invention also provides a detection instrument containing the detection test strip.

The invention contains the test strip/instrument of the above-mentioned electrode, especially the test strip/instrument used for detecting the blood sample; particularly a test strip/instrument for the detection of prothrombin time.

Compared with the prior art, the invention has the following beneficial effects:

1. the invention adopts an electrode system with a special structure, and utilizes the thickness and the hydrophobicity of the reference electrode to ensure that the reference electrode not only participates in electrochemical reaction, but also serves as a limiting component of a reaction reagent, so that the reaction reagent can form a uniform dry reagent film after being spotted on the working electrode, thereby improving the repeatability of a reaction signal of a test strip.

2. Since the reactive reagent can be uniformly solidified on the surface of the working electrode, when the blood sample flows into the reaction area and reacts with the reagent in the dry reagent film, the generated oxidizable substance can quickly and uniformly flow onto the surface of the working electrode to be oxidized, so that the oxidation reaction efficiency is higher and the repeatability is good.

3. The electrode material adopted by the invention has low cost and can be printed on the base material by a silk-screen printing process, so the test strip has low production cost and can greatly reduce the burden of diagnosis and medical treatment cost.

Drawings

FIG. 1: the invention relates to a substrate with a circular electrode.

FIG. 2: the invention relates to a substrate with square electrodes.

FIG. 3: example 1 schematic representation of a substrate after spotting and drying of reagents.

FIG. 4: a simulated explosion plot of a typical test strip of the present invention.

FIG. 5: an explosion diagram of a test strip of the present invention.

FIG. 6: another test strip of the present invention is a schematic explosion diagram (with a raised pad).

FIG. 7: prothrombin time test response curve; FIG. 7a shows the reaction current curve measured with the electrode system of the present invention, and FIG. 7b shows the reaction current curve measured with the conventional electrode system (parallel arrangement of the electrode systems).

FIG. 8: the test strip structure of the prior art (CN 2788184Y).

Detailed Description

To further explain the technical means and effects of the present invention adopted to achieve the intended purpose, the following detailed description of the embodiments, structures, features and effects according to the present invention will be given with reference to the accompanying drawings and preferred embodiments.

Example 1

As shown in fig. 1, the electrode is supported on an insulating substrate 3. The substrate 3 used may be any insulating material, such as plastic PET, ABS, PC, etc. Because the two electrodes are made of different materials, the two electrodes can be printed on the substrate in two times, the printing sequence does not matter, and only the second electrode is printed after the drying of printing.

The working electrode 321 is a circular sheet structure, and the material is selected from carbon; the reference electrode 322 is in the shape of a circular ring with an opening, and the material is selected from silver/silver chloride; the working electrode 321 is connected to a first conductive contact plate 325 by a conductive wire 323, the conductive wire 323 being routed through an opening of the reference electrode 322; a reference electrode 322 in the shape of a circular ring (which may also be provided with a small protrusion at any position on the circumference of the ring to facilitate connection of the conductive wire, although it is also possible if no small protrusion is provided) is connected to the second conductive contact plate 326 via a conductive wire 324. The conductive contact plate is used to connect the test strip to the current sensing circuitry in the analyzer. The oxidation current generated at the working electrode flows through conductive wire 323 to conductive contact plate 325 and then to the current sensing circuitry in the analyzer, and the current loop is completed through conductive contact plate 326, conductive wire 324 and reference electrode 322.

Product parameters are as follows:

opening width: 1mm

The inner diameter of the circular ring is 2mm, and the outer diameter of the circular ring is 3 mm;

the diameter of the circular working electrode was 2 mm.

The circular working electrode and the reference electrode with the non-closed ring structure both have certain thicknesses, and the thicknesses are 0.01mm and 0.05mm respectively.

Example 2

The only difference between the embodiment 2 shown in fig. 2 and the above embodiment 1 is that the shape of the electrode is changed from round to square, and the manufacturing process and the working principle of the two are not different. When the electrodes are printed, the round structure on the printing template is changed into a square shape.

The working electrode 321 is a square sheet structure, and the material is selected from carbon; the reference electrode 322 has a square shape with one opening, and the material is selected from silver/silver chloride; the working electrode 321 is connected to a first conductive contact plate 325 by a conductive wire 323, the conductive wire 323 being routed through an opening of the reference electrode 322; a reference electrode 322 in the form of a square (optionally provided with a small protrusion at any location on the square to facilitate connection of the conductive wire, but of course it is also possible if no small protrusion is provided) is connected to a second conductive contact plate 326 via a conductive wire 324. The conductive contact plate is used to connect the test strip to the current sensing circuitry in the analyzer. The oxidation current generated at the working electrode flows through conductive wire 323 to conductive contact plate 325 and then to the current sensing circuitry in the analyzer, and the current loop is completed through conductive contact plate 326, conductive wire 324 and reference electrode 322.

The two embodiments are only used to illustrate two specific examples of the present invention, and other shapes of electrodes, such as triangle, oval, trapezoid, etc., are also within the scope of the present invention. However, the circular electrode shown in example 1 is preferred because the circular structure is more suitable for spotting of reagents and the dried reagent film after curing is more uniform.

Example 3

Figure 3 shows a dry reagent film after spotting and drying of reagents on the basis of example 1. The reagent mixture is usually spotted in the center of the working electrode, and due to its flow characteristics, the reagent mixture will automatically flow from the center to the periphery until the inner peripheral edge of the reference electrode 322 stops flowing. After natural air drying and baking, a dry reagent film 327 is formed on and around the surface of the working electrode.

When a blood sample is applied to the reaction area, a coagulation reaction will occur on the surface of the dry reagent film 327, and thus the generated oxidizable substance can rapidly flow to the surface of the working electrode (hidden under the dry reagent film 327 in the figure, not shown) through the microporous channel on the dry reagent film to be oxidized to generate an oxidation current.

Example 4

Fig. 4 shows an exploded view of a test strip containing an electrode of the present invention.

I.e., the structure used for the liquid sample test strip. The constituent elements of the liquid sample test strip include a cover plate 1, a channel plate 2, and a base plate 3.

The substrate 3, i.e., the insulating substrate as in example 1, on which the electrode as in example 1 is supported.

The cover plate 1 is a panel having a sample inlet 11 for collecting a blood sample, for example, in a needle-prick blood collecting operation, after a finger of a subject receives a needle prick and extrudes a proper amount of blood, a bleeding position is set at a sample inlet, and then the blood sample flows into a sample inlet cavity of a next plate and a channel plate and reaches a circulation hole along with the channel. The circulation holes communicate with the position where the electrode of the next plate, i.e., the insulating substrate, is located. So that the coagulation reaction is carried out in the reaction area defined by the electrode pair and the generated oxidizable substance is oxidized to generate a current signal to be detected.

Example 5

FIG. 5 further shows the test strip of the present invention containing the preferred cover plate structure in the form of a line graph.

Wherein, the sampling hole 11 is arranged at the left end of the cover plate 1, and the gas outlet 12 is arranged at the right end of the cover plate 1. The channel plate 2 is provided with a sample introduction chamber 21, grooves as liquid flow channels 22 and flow holes 23. The grooves are hollowed out, when the upper surface and the lower surface of the channel plate are respectively overlapped with the cover plate 1 and the base plate 3, a space defined by the upper surface and the lower surface and the base plate 3 together forms a flow pipeline, one side wall of the pipeline is the lower surface of the cover plate, and the other side wall of the pipeline is the upper surface of the base plate 3. Wherein, the sample injection cavity 21 is arranged at the left end of the channel plate 2, and when the cover plate 1 is stacked on the channel plate 2, the sample injection cavity 21 is located right below the sample injection hole 11 in the cover plate 1.

In addition, the sample chamber 21 and the flow hole 23 are connected by a liquid flow channel 22, so that liquid can flow from the sample chamber 21 into the flow hole 23 through the liquid flow channel 22. The flow hole 23 extends with an extension duct 24 of the liquid flow channel 22 opposite to the far end of the sample feeding cavity 21. The air outlet 12 of the cover plate 1 is located right above the end of the extension duct 24, and the ventilation opening defined by the channel plate 2 is located at the end of the extension duct 24, so that the extension duct 24 communicates with the outside through the ventilation opening defined by the air outlet 12.

In the present embodiment, the liquid flow channel 22 is a hollow channel, and specifically, is a channel formed by the space defined by the cover plate 1 and the base plate 3 when the cover plate 1 and the base plate 3 are stacked on the upper and lower surfaces of the channel plate 2, respectively.

The substrate 3 carries a reaction zone 31 in which the electrodes of the invention are accommodated (not shown in detail in this figure, see the electrodes of examples 1-3). The reaction zone 31 is located directly below the flow holes 23 of the channel plate 2.

The components are sequentially stacked from bottom to top in a movable stacking mode through the cover plate 1, the channel plate 2 and the substrate 3 which are arranged as above to form the liquid sample detection test strip.

In order to induce the liquid sample to flow into the reaction region 31 more rapidly to effect the reaction, in a preferred embodiment, the reaction region 31 comprises a hydrophilic material, or the reaction region 31 is made at least partially of a hydrophilic material.

In a more preferred embodiment, at least one of the four tube walls of the liquid flow channel 22 (e.g., two sidewalls of the hollow groove and the cover plate 1, the substrate 3 and the hollow groove, or three tube walls of the non-hollow groove and the cover plate 1 and the non-hollow groove) is made of a hydrophilic material; of course, in another alternative embodiment, at least the liquid flow conduit at least partially comprises, or is partially made of, a hydrophilic material; this is better when all of the four tube walls are made of hydrophilic material.

In order to prevent the liquid sample from flowing out of the gas outlet 12 from the extension pipe 24, which affects the quality of the reaction, in a preferred embodiment, the extension pipe 24 comprises, or is at least partially made of, a hydrophobic material; a hydrophobic material is present near the outlet portion and a hydrophilic material is present near the flow-through hole portion.

When the device is used, a liquid sample to be detected is input into the sample inlet 11, the liquid sample flows into the sample inlet cavity 21 from the sample inlet 11, and the liquid sample flows into the reaction area 31 through the liquid flow channel 22 under the action of the hydrophilic material of the cover plate 1, and in the process, as the air vent at the tail end of the extension pipeline 24 is communicated with the outside through the air outlet 12 on the cover plate 1, the liquid can flow forwards in the liquid flow channel 22. When the reaction area 31 is filled with the liquid sample to be tested, the liquid sample will then flow forward into the extension pipe 24 until the hydrophobic portion or the air outlet 12 in the extension pipe is stopped by its hydrophobic interaction. If the viscosity of the liquid sample is large, the liquid sample may stop flowing before reaching the hydrophobic portion or the air outlet 12 because the tensile force generated by the hydrophilic action of the cover plate 1 and the flow resistance of the liquid sample are balanced at this time. The liquid sample test strip is inserted into the test meter such that the electrodes are energized. At this time, the liquid sample and the reaction reagent react with each other in the energized electrode.

When the liquid sample to be tested flows into the reaction area, the blood coagulation reaction will occur on the surface of the dry reagent membrane, and the generated oxidizable substance can rapidly flow to the surface of the working electrode through the micropore channel on the dry reagent membrane to be oxidized to generate an oxidation current.

Example 6

The prothrombin time test example was carried out using the test strip of example 4. The test strip is used in conjunction with an analyzer, which functions include: 1) applying a direct current voltage between the working electrode and the reference electrode; 2) detecting a current between the two electrodes; 3) recording the curve of the measured current along with the change of time; 4) the prothrombin time is calculated by analyzing the current-time curve. An analyzer equipped with a commercially available prothrombin time measuring device can be used.

FIG. 7a shows a set of reaction current curves measured with the electrode system of the present invention, and FIG. 7b shows a set of reaction current curves measured with a conventional electrode system (parallel arrangement of electrode systems). Comparing the two sets of curves, the electrode system of the present invention is significantly superior to the prior electrode system in terms of reproducibility, with a CV of 5% for the electrode system of the present invention and a CV of 20% for the prior system. And the optimization is produced under the condition of reducing the production cost of equipment (only carbon is used as an electrode material, and the cost is low).

The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.

Claims

1. An electrode system comprising at least two electrodes, one of said electrodes being a working electrode and the other of said electrodes being a reference electrode; the working electrode is of a sheet structure, and the reference electrode comprises a non-closed ring structure arranged around the working electrode; the sheet structure is regular and round; the non-closed ring structure is a regular circular ring, the thickness of the reference electrode is 0.05-0.5 mm, the reference electrode and the working electrode are arranged concentrically, the surface of the substrate within the inner diameter of the reference electrode and the surface of the working electrode are loaded with chemical reagents, and the reference electrode is used as a limiting part of the chemical reagents.

2. The electrode system of claim 1, wherein the non-closed loop structure is annular in shape with an opening.

3. The electrode system of claim 1, wherein the material of the working electrode is selected from the group consisting of an inert metal or carbon; the material of the reference electrode is silver/silver chloride.

4. The electrode system of claim 3, wherein the working electrode material is one or more of gold, platinum, rhodium, and carbon.

5. The electrode system of claim 1, wherein the reference electrode has an inner diameter of 1mm to 10mm and an outer diameter of 2mm to 12 mm; the diameter of the working electrode is 0.5 mm-9 mm.

6. The electrode system of claim 1, wherein the working electrode has a thickness of 0.01mm to 0.1 mm.

7. A substrate comprising an electrode system according to any one of claims 1 to 6, wherein the electrodes are supported on the substrate, and the substrate is an insulating material.

8. The substrate of claim 7, wherein the substrate further comprises two conductive wires connecting the working electrode and the reference electrode, respectively.

9. The substrate of claim 8, wherein the two conductive wires are connected to two conductive contact plates, respectively.

10. The substrate of claim 9, wherein the reference electrode is further provided with a protrusion at any position of the non-closed loop structure, and the protrusion is used for connecting a conductive wire.

11. A test strip comprising the electrode system of any one of claims 1-6, wherein the test strip is an insulating substrate having the electrodes supported on the surface thereof.

12. The test strip of claim 11, wherein the chemical reagent is formed by spotting and drying a liquid reagent that is confined within the inner diameter of the reference electrode when spotted.

13. The test strip of claim 11, wherein the test substance is a liquid sample.

14. The test strip of claim 13, wherein the fluid sample is a blood sample.

15. The test strip of claim 11, further comprising a channel plate on the base plate, and a cover plate on the channel plate; the channel plate is provided with a channel plate hollow structure which is positioned above the non-closed ring structure and has an area larger than that of the non-closed ring structure;

the space defined by the hollow structure of the channel plate and positioned on the substrate is a reaction area;

or, the test strip also comprises a raised sheet positioned on the base plate, a channel plate positioned on the raised sheet, and a cover plate positioned on the channel plate; the heightening sheet is provided with a hollow structure of the heightening sheet, the hollow structure of the heightening sheet is positioned above the non-closed ring structure, and the area of the hollow structure of the heightening sheet is larger than that of the non-closed ring structure; the channel plate is provided with a channel plate hollow structure corresponding to the heightening piece hollow structure in position; the space defined by the hollow-out structures of the heightening pieces and positioned on the substrate is a reaction area.

16. The test strip of claim 11, wherein the test strip is a clotting test strip.

17. The test strip of claim 15, wherein the cover plate has a sample inlet at one end and an outlet at the other end; the channel plate is provided with a sample injection cavity, a liquid circulation channel and a circulation hole, wherein when the cover plate is stacked on the channel plate, the sample injection cavity is positioned below the sample injection hole and is connected with the circulation hole through the liquid circulation channel, the circulation hole of the channel plate is also connected with an extension pipeline, the extension direction of the extension pipeline is opposite to the other side of the sample injection cavity and the liquid circulation pipeline, when the cover plate is stacked on the channel plate, the channel plate defines a ventilation port communicated with the outside through an air outlet, the ventilation port is positioned at any point of the extension pipeline, or at least part of the ventilation port is in contact with the extension pipeline.

18. The test strip of claim 17, wherein the vent has an aperture diameter of 0.1mm to 5 mm.

19. The test strip of claim 17, wherein the ratio of the cross-sectional area of the extension conduit to the cross-sectional area of the fluid flow channel is from 1:1 to 1: 10.

20. The test strip of claim 17, wherein the ratio of the length of the extension conduit to the length of the fluid flow channel is from 1:1 to 1: 10.

21. The test strip of claim 17, wherein the walls of the fluid communication channel are at least partially hydrophilic, and the hydrophilic sites extend through both ends of the fluid communication channel.

22. The test strip of claim 17, wherein the wall of the extension conduit is at least partially hydrophobic.

23. The test strip of claim 22, wherein the wall of the extension tube is a hydrophobic material adjacent the outlet portion and the wall of the extension tube is a hydrophilic material adjacent the flow-through aperture portion.

24. The test strip of claim 22, wherein the length of the portion of hydrophilic material is 1-2 mm.

25. The test strip of claim 17, wherein the sample inlet chamber, the fluid flow channel, the flow port, the extension conduit, and the gas vent are all in the same line.

26. A test instrument comprising the test strip of any one of claims 11-25; it is characterized in that the instrument is a prothrombin time detection instrument.